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Exploring the folding landscape of a structured RNA
Rick Russell1, Xiaowei Zhuang, Hazen P Babcock
1Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
Summary
Researchers mapped the Tetrahymena ribozyme folding landscape, revealing distinct pathways separated by energy barriers. Specific RNA structural features dictate pathway selection, influencing folding efficiency.
Area of Science:
- Molecular Biology
- Biophysics
- Structural Biology
Background:
- Structured RNAs fold via complex energy landscapes to reach active states.
- Understanding these landscapes is crucial for RNA function and design.
Purpose of the Study:
- To investigate the folding landscape topology of the Tetrahymena ribozyme.
- To identify structural determinants of distinct folding pathways.
Main Methods:
- Single-molecule ribozyme folding experiments initiated from defined landscape regions.
- Small-angle X-ray scattering (SAXS) for structural insights.
- Chemical protection and mutagenesis assays to probe structural features.
Main Results:
- Identified discrete folding pathways within the Tetrahymena ribozyme landscape.
- Demonstrated large free-energy barriers separating these pathways, suggesting deep, stable channels.
- Showed that a specific long-range tertiary contact's role (aiding or hindering folding) depends on its formation timing.
Conclusions:
- The Tetrahymena ribozyme folding landscape is topographically complex with distinct, kinetically trapped pathways.
- Specific RNA structural elements, particularly tertiary contacts, critically control pathway selection and folding dynamics.
- Provides unprecedented insight into RNA folding landscape topology and its underlying structural basis.